Fractional CO₂-assisted topical delivery of tofacitinib as an effective modality for refractory nail psoriasis

Dear Editor,

Nail psoriasis (NP) can be challenging to treat, especially in its isolated form. Patients on systemic treatment for psoriasis may require an additional topical or intralesional modality for NP. Unfortunately, there are few available and effective topical modalities for this disease. Calcipotriol and betamethasone dipropionate combination and tazarotene 0.1% are topicals that have been used for NP with variable efficacy. Topical tofacitinib, which is a Janus kinase (JAK) inhibitor, has been used in cutaneous psoriasis but very sparingly in NP.¹

A 38-year-old male (Patient 1) presented with coarse nail pitting suggestive of nail matrix related psoriasis. Nail disease was refractory to conventional topical agents, including topical steroids and retinoids, which were given for 6 months. Patient 2 was a 44-year-old male who presented with nail matrix related psoriasis predominantly in the form of crumbling of the nail plate and coarse nail pitting. Prior treatment with conventional topical agents such as Topical tazarotene 0.1% gel and combination of clobetasol propionate 0.05% with calcipotriol 0.005% ointment was used twice daily for 6 months without improvement in nail pitting did not give adequate results. Both patients were then treated with a combination of fractional CO₂ laser and topical tofacitinib. After 45 minutes of topical anaesthesia, fractional CO₂ (Futura RF 50, Dermaindia®) treatment was administered primarily over the nail plate overlying the lunula and proximal nail fold (Power 12W, Energy 18mJ, pulse duration 1.5ms, 2 passes). Topical 2% tofacitinib ointment was applied immediately after the procedure under occlusion. The patient was advised to continue the topical treatment once daily under occlusion. Fractional CO₂ was done for a total of 3 sittings at an interval of 4 weeks. Treatment response was assessed at baseline and at each visit by modified nail psoriasis severity index (mNAPSI) scores. At 12 weeks of treatment, patient 1 showed a reduction in mNAPSI from a baseline score of 5/96 to 1/96 [Figure 1a and 1b], and patient 2 showed a reduction in mNAPSI from a baseline score of 7/96 to 3/96 [Figure 2a and 2b]. The treatment was well-tolerated in both patients with no significant adverse effects. Findings have been summarised in Table 1. Dermoscopy (Heinz Delta,10x) [Supplementary Figure 1a and 1b] revealed coarse irregular pitting in patient 1 along with crumbling of the nail plate in patient 2 [Supplementary Figure 2a and 2b] which showed marked improvement after 3 sittings for fractional Co2 with tofacitinib [Supplementary Figure 1 and 2 respectively].

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Figure 1a:

Coarse and irregular pitting seen over nail plate with mNAPSI of 5/96 in patient 1.

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Figure 1b:

Marked improvement in nail matrix changes (mNAPSI-1/96) after 3 sittings of fractional CO₂ laser with topical tofacitinib 2% ointment.

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Figure 2a:

Crumbling and irregular pitting seen over nail plate with mNAPSI of 7/96 in patient 2.

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Figure 2b:

Marked improvement in nail matrix changes (mNAPSI- 3/96) after 3 sittings of fractional CO₂ laser with topical tofacitinib 2% ointment.

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NP can be a difficult disease to treat. Various intralesional, topical, and systemic agents have been used for NP management. With isolated NP involving less than three nails and having only nail matrix involvement (as seen in our case), steroid or methotrexate injections are proposed to be the first line treatment modality.² However, they might be unacceptable to many patients due to the invasive nature of the procedure and possible pain during administration. Second-line treatments include topical agents such as steroids, retinoids like tazarotene, and calcipotriol.² However, penetration of topical agents to the nail matrix is hindered by the proximal nail fold, which reduces its efficacy.

Fractional CO₂ has been used in NP as a method of trans-ungual drug delivery and for the remodelling of the nail unit.³ The depth of penetration correlates with the laser fluence and has been found to be approximately 150-200 micrometer.⁴ It has also been used in combination with other topicals, including steroids, tazarotene, and methotrexate, with moderate efficacy in NP.^3,5,6 However, these agents can have side effects such as irritation of the nail folds, atrophy, and hypopigmentation.¹ We used a unique combination of fractional CO₂ with tofacitinib 2 % ointment for the management of NP. Tofacitinib is a non-specific JAK inhibitor targeting mainly JAK 1 and 3. It helps in normalise the interleukin-23/T-helper 17 axis, thereby limiting psoriatic inflammation.¹ Its enhanced penetration in two cases of nail matrix psoriasis with the help of fractional CO₂ showed good clinical efficacy. In both patients, the treatment was well-tolerated without any significant adverse effects. Fractional CO₂-assisted delivery of topical tofacitinib may be considered as an alternative therapeutic option in refractory cases of NP. Future controlled studies with a larger sample size will provide more conclusive evidence.